PEARL (CML1624) = Asciminib in Early Treatment of CML [Spain, Italy]

What is the purpose of the study

This study will investigate the efficacy and the safety of asciminib at a dose of 80 mg once daily as single agent or 40 mg twice daily in combination with nilotinib 300 mg twice daily as early treatment for adult patients with newly diagnosed chronic-phase chronic myeloid leukemia (CML-CP).

What will happen during the study

Patients will receive either asciminib at a dose of 80 mg by mouth once daily as single agent (treatment arm A) or asciminib 40 mg by mouth twice daily plus nilotinib 300 mg by mouth twice (treatment arm B) for a minimum of 2 years. During the following 2 years, asciminib will be continued at the same dose in both arms; in the combination arm (arm B) the nilotinib dose will be reduced to 300 mg daily.

Patients maintaining a stable MR4 up to the end of the fourth year will discontinue the treatment.

Key inclusion criteria

This study includes patients of all sexes who:

• are aged 18 years or older.
• have a cytogenetic and molecular confirmed diagnosis of Philadelphia chromosome (Ph+) and BCR::ABL1 positive CML.
• are in early chronic phase, less than 3 months from diagnosis.
• have evidence of typical BCR::ABL1 RNA transcripts e13a2 or e14a2 (b2a2 or b3a2) at the time of study entry .
• have been treated with any tyrosine kinase inhibitor (TKI) for 30 days or less. Prior treatment with hydroxyurea or anagrelide is allowed.
• have an Eastern Co-Operative Group (ECOG) status of 0, 1 or 2.
• have adequate end organ function as defined in the study protocol.

Further criteria may apply. Please discuss these with your doctor or study staff.

Key exclusion criteria

This study does not include patients who:

• have CML in blast phase (BP) or in second chronic phase after previous BP, according to WHO criteria.
• have been treated with TKIs for more than 30 days.
• have a history or current diagnosis of heart disease indicating significant risk of safety for patients participating in the study.
• have a severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. uncontrolled diabetes, active or uncontrolled infection).
• have had acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis.
• have a history of acute or chronic liver disease.
• have a history of other active malignancy within 2 years prior to study entry except for previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively.

Further criteria may apply. Please discuss these with your doctor or study staff.

Estimated primary completion date

Where can I find additional information

You can find a study description in the US register ClinicalTrials.gov. This is a database provided by the U. S. National Institutes of Health.

You can also find a study description in the Clinical Trials Information System (CTIS) . This is a database hosted by the European Medicines Agency (EMA).

Study centers / principal investigators

Spain

Badalona
Institut Catala D’oncologia
Contact: Dr. Blanca Xicoy Cirici

Barcelona
Hospital del Mar
Contact: Dr Patricia Vélez Tenza

Bilbao
Hospital Universitario Basurto
Contact: Dr. Fernando Marco de Lucas

Girona
Institut Català d’Oncologia
Contact: Dr. Anna Angona Figueras

Granada
Hospital Universitario Virgen de las Nieves
Contact: Dr. José Manuel Puerta

Las Palmas De Gran Canaria
Hospital Universitario de Gran Canaria Dr. Negrín
Contact: Maria Teresa Gómez Casares

Leon
Dr. Valentin Garcia-Gutiérrez
Contact: Dr. Natalia de las Heras Rodríguez

Madrid
Hospital Gral Universitario Gregorio Marañón
Contact: Santiago Osorio Prendes

Madrid
Hospital Universitario 12 de Octubre
Contact: Dr. Gonzalo Carreño Gómez-Tarragona

Madrid
Hospital Universitario Ramon Y Cajal
Contact: Dr. Valentin Garcia-Gutiérrez

Madrid
Hospital Universitario La Paz
Contact: María Raquel de Paz Arias

Murcia
Hospital Clínico Universitario Virgen de la Arrixaca
Contact: Dr. Raul Perez Lopez

Salamanca
Complejo Asistencial Universitario de Salamanca
Contact: Dr. Magdalena Sierra Pacho

Santiago De Compostela
Complexo Hospitalario Universitario De Santiago
Contact: Dr. Manuel Mateo Pérez Encinas

Valencia
Hospital Universitario Y Politecnico La Fe
Contact: Dr. Elvira Mora Casterá

Italy

Ancona
Azienda Ospedaliero Universitaria Delle Marche
Contact: Dr. Anna Rita Scortechini

Bari
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
Contact: Prof. Pellegrino Musto

Bologna
Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
Contact: Prof. Fausto Castagnetti

Brescia
Azienda Socio Sanitaria Territoriale Degli Spedali Civili Di Brescia
Contact: Dr. Mariella D’Adda

Catania
Azienda Ospedaliero-Universitaria Policlinico G. Rodolico-San Marco Di Catania
Contact: Dr. Uros Markovic

Florence
Careggi University Hospital
Contact: Dr. Barbara Scappini

Messina
Azienda Ospedaliera Universitaria Gaetano Martino Messina
Contact: Prof. Alessandro Allegra

Milan
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
Contact: Dr. Alessandra Iurlo

Naples
Azienda Ospedaliera Di Rilievo Nazionale Antonio Cardarelli
Contact: Dr. Mario Annunziata

Naples
Azienda Ospedaliera Universitaria Federico II Di Napoli
Contact: Prof. Fabrizio Pane

Novara
Azienda Ospedaliero-Universitaria Maggiore Della Carita
Contact: Dr. Andrea Patriarca

Padova
Azienda Ospedaliera di Padova
Contact: Dr. Gianni Binotto

Pavia
Fondazione IRCCS Policlinico San Matteo
Contact: Dr. Chiara Elena

Palermo
Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
Contact: Dr. Alessandra Malato

Palermo
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
Contact: Dr. Marco Santoro

Piacenza
Azienda Unita Sanitaria Locale Di Piacenza
Contact: Dr. Elena Trabacchi

Reggio Calabria
Grande Ospedale Metropolitano Bianchi Melacrino Morelli
Contact: Dr. Matteo Picilli

Reggio Emilia
Azienda USL IRCCS Di Reggio Emilia
Contact: Dr. Isabella Capodanno

Rome
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Contact: Dr. Federica Sorà

Rome
Azienda Ospedaliero-Universitaria Policlinico Umberto I
Contact: Dr. Massimo Breccia

Siena
Azienda Ospedaliera Universitaria Senese
Contact: Prof. Monica Bocchia

Turin
Azienda Ospedaliera Ordine Mauriziano Di Torino
Contact: Contact: Prof. Carmen Fava

Turin
Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
Contact: Dr. Valentina Giai

Udine
Azienda Sanitaria Universitaria Friuli Centrale
Contact: Dr. Mario Tiribelli

Verona
Azienda Ospedaliera Universitaria Integrata Verona
Contact: Prof. Massimiliano Bonifacio

Vicenza
Azienda Unita Locale Socio Sanitaria N 8 Berica
Contact: Dr. Davide Facchinelli